IP3 Receptor Plasticity Underlying Diverse Functions
Kozo Hamada1, Katsuhiko Mikoshiba1
1Laboratory of Cell Calcium Signaling, Shanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, Shanghai, 201210, China; email: hamada@shanghaitech.edu.cn, mikosiba@shanghaitech.edu.cn.
Annual Review of Physiology
|November 16, 2019
Summary
Inositol 1,4,5-trisphosphate receptors (IP3Rs) release calcium ions, crucial for cell function. Recent structural studies reveal how IP3R plasticity regulates diverse cellular processes and diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Cellular Physiology
Background:
- Extracellular stimuli generate inositol 1,4,5-trisphosphate (IP3), an intracellular signal.
- IP3 binds to the IP3 receptor (IP3R) to release calcium ions (Ca2+) from the endoplasmic reticulum.
- IP3R's diverse functions and associated genetic disorders are increasingly understood.
Purpose of the Study:
- To review recent advancements in IP3R structure and function.
- To elucidate the mechanisms of IP3-dependent calcium release and regulation.
- To explore the role of protein plasticity in IP3R-mediated cellular functions.
Main Methods:
- Cryo-electron microscopy
- X-ray crystallography
- Functional studies
Main Results:
- Resolved structures of IP3R provide insights into IP3 binding and Ca2+ release.
- Allosteric gating and assembly transformations in IP3R are linked to structural changes.
- Protein plasticity enables IP3R to regulate functions at cellular microdomains.
Conclusions:
- Recent structural and functional studies have advanced our understanding of IP3R.
- IP3R's protein plasticity is key to its diverse roles in cellular physiology and pathophysiology.
- Further research into IP3R structure-function relationships can illuminate disease mechanisms.
Keywords:
Ca2+ channelallosteric regulationendoplasmic reticulumgating mechanisminositol 1,4,5-trisphosphateinositol 1,4,5-trisphosphate receptorMore Related Videos
Related Concept Videos
01:11IP3/DAG Signaling Pathway
14.1K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
14.1K
01:42Phosphoinositides and PIPs
10.0K
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
10.0K
01:15Amplifying Signals via Second Messengers
8.2K
Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
8.2K
01:31Regulation of the Unfolded Protein Response
2.9K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.9K
01:17Intracellular Signaling Affects Focal Adhesions
3.4K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
3.4K
01:09GPCRs Regulate Adenylyl Cylase Activity
7.1K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
7.1K